Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.

41 With respect to cardiovascular mortality, which showed a nonsignificant trend toward reduction with treatment, several reasons may have contributed to an underestimation of observed treatment effects, including the limited number of events and thus statistical power, adjudication biases, along with substantial heterogeneity in definitions of cardiovascular mortality and safety outcomes in included RCTs.

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In addition, there was a trend toward reduced cardiovascular mortality (15 RCTs; OR: 0.84; 95% CI: 0.71–1.01; p = 0.06; I 2 = 0%; Figure 3(b) ), which did not reach statistical significance (summarized outcomes in Table 2 ).

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